6. Glycemic Targets: Standards of Care in Diabetes—2023

In the paper

“No study to date has reported a decrease in level 3 hypoglycemia.”

In the paper

“Another genetic variant, X-linked glucose-6-phosphate dehydrogenase G202A, carried by 11% of African American individuals, was associated with a decrease in A1C of about 0.8% in hemizygous men and 0.7% in homozygous women compared with those without the trait (20).”

What the sources say

• Not checked yetcites [20] Wheeler, 2017, Impact of common genetic determinants of hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: a transethnic genome-wide meta-analysis, PLoS Med source

In the paper

“the international A1C-Derived Average Glucose (ADAG) study, which assessed the correlation between A1C and frequent BGM and CGM in 507 adults (83% non-Hispanic White) with type 1, type 2, and no diabetes (13)”

What the sources say

• Not checked yetcites [13] Nathan, 2008, Translating the A1C assay into estimated average glucose values, Diabetes Care source

In the paper

“In a report, mean glucose measured with CGM versus central laboratory-measured A1C in 387 participants in three randomized trials demonstrated that A1C may underestimate or overestimate mean glucose in individuals (12).”

What the sources say

• Not checked yetcites [12] Beck, 2017, The fallacy of average: how using HbA1C alone to assess glycemic control can be misleading, Diabetes Care source

In the paper

“Taken together, A1C and glucose parameters are essential for the optimal assessment of glycemic status.”

In the paper

“However, most assays in use in the U.S. are accurate in individuals who are heterozygous for the most common variants (ngsp. org/interf.asp).”

What the sources say

• Not checked yetcites ngsp. org/interf.asp

In the paper

“Other studies have also demonstrated higher A1C levels in African American participants than in White participants at a given mean glucose concentration (15,16).”

What the sources say

• Not checked yetcites [15] Selvin, 2016, Are there clinical implications of racial differences in HbA1c? A difference, to be a difference, must make a difference, Diabetes Care source
• Not checked yetcites [16] Bergenstal, 2017, Racial differences in the relationship of glucose concentrations and hemoglobin A1c levels, Ann Intern Med source

In the paper

“Individuals on a variety of insulin treatment plans can benefit from CGM with improved glucose control, decreased hypoglycemia, and enhanced self-efficacy (Section 7, “Diabetes Technology”) (1).”

What the sources say

• Not checked yetcites [1] Deshmukh, 2020, Effect of flash glucose monitoring on glycemic control, hypoglycemia, diabetes-related distress, and resource utilization in the Association of British Clinical Diabetologists (ABCD) nationwide audit, Diabetes Care source

In the paper

“In contrast, a recent report in Afro-Caribbean individuals found lower A1C relative to glucose values (17).”

What the sources say

• Not checked yetcites [17] Khosla, 2021, HbA1c performance in african descent populations in the United States with normal glucose tolerance, prediabetes, or diabetes: a scoping review, Prev Chronic Dis source

In the paper

“For example, conditions that affect red blood cell turnover (hemolytic and other anemias, glucose-6-phosphate dehydrogenase deficiency, recent blood transfusion, use of drugs that stimulate erythropoiesis, endstage kidney disease, and pregnancy) may result in discrepancies between the A1C result and the patient's true mean glycemia (11).”

What the sources say

• Not checked yetcites [11] Kidney Disease: Improving Global Outcomes (KDIGO) Diabetes Work Group, 2020, KDIGO 2020 clinical practice guideline for diabetes management in chronic kidney disease, Kidney Int source

In the paper

“A 14-day CGM assessment of TIR and GMI can serve as a surrogate for A1C for use in clinical management (5)(6)(7)(8)(9).”

What the sources say

• Not checked yetcites (5)(6)(7)(8)(9)

In the paper

“The test is the primary tool for assessing glycemic control and has a strong predictive value for diabetes complications (2)(3)(4).”

What the sources say

• Not checked yetcites (2)(3)(4)

In the paper

“Limitations in perfect alignment between glycemic measurements do not interfere with the usefulness of BGM/CGM for insulin dose adjustments.”

In the paper

“The test is the primary tool for assessing glycemic control and has a strong predictive value for diabetes complications (2)(3)(4).”

What the sources say

• Not checked yetcites (2)(3)(4)

In the paper

“Such analyses suggest that, on a population level, the greatest number of complications will be averted by taking patients from very poor control to fair/good control.”

In the paper

“These trials showed that lower A1C levels were associated with reduced onset or progression of some microvascular complications (50)(51)(52).”

What the sources say

• Not checked yetcites (50)(51)(52)

In the paper

“In recent years, CGM has become a standard method for glucose monitoring for most adults with type 1 diabetes (34).”

What the sources say

• Not checked yetcites [34] Holt, 2021, The management of type 1 diabetes in adults. A Consensus report by the American Diabetes Association (ADA) and the European Association for the Study of Diabetes (EASD), Diabetes Care source

In the paper

“Long-term follow-up of the UKPDS cohorts showed enduring effects of early glycemic control on most microvascular complications (47).”

What the sources say

• Not checked yetcites [47] Holman, 2008, 10-year follow-up of intensive glucose control in type 2 diabetes, N Engl J Med source

In the paper

“Setting goals by face-to-face or remote consultations has been shown to be more effective than usual care for glycemic control in type 2 diabetes for fasting plasma glucose and glycated hemoglobin (41).”

What the sources say

• Not checked yetcites [41] Whitehead, 2022, The effectiveness of goal setting on glycaemic control for people with type 2 diabetes and prediabetes: a systematic review and meta-analysis, J Adv Nurs source

In the paper

“Findings from the DCCT (33) and UKPDS (49) studies demonstrate a curvilinear relationship between A1C and microvascular complications.”

What the sources say

• Not checked yetcites [33] Diabetes Control and Complications Trial Research Group, 1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med source
• Not checked yetcites [49] Adler, 2000, Association of systolic blood pressure with macrovascular and microvascular complications of type 2 diabetes (UKPDS 36): prospective observational study, BMJ source

In the paper

“The Kumamoto Study (44) and UK Prospective Diabetes Study (UKPDS) (45,46) confirmed that intensive glycemic control significantly decreased rates of microvascular complications in people with short-duration type 2 diabetes.”

What the sources say

• Not checked yetcites [44] Ohkubo, 1995, Intensive insulin therapy prevents the progression of diabetic microvascular complications in Japanese patients with non-insulin-dependent diabetes mellitus: a randomized prospective 6-year study, Diabetes Res Clin Pract source
• Not checked yetcites [45] UK Prospective Diabetes Study (UKPDS) Group, 1998, Effect of intensive blood-glucose control with metformin on complications in overweight patients with type 2 diabetes (UKPDS 34), Lancet source
• Not checked yetcites [46] UK Prospective Diabetes Study (UKPDS) Group, 1998, Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33), Lancet source

In the paper

“Major clinical trials of insulin-treated patients have included BGM as part of multifactorial interventions to demonstrate the benefit of intensive glycemic control on diabetes complications (33).”

What the sources say

• Not checked yetcites [33] Diabetes Control and Complications Trial Research Group, 1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med source

In the paper

“The implication of these findings is that there is no need to deintensify therapy for an individual with an A1C between 6 and 7% in the setting of low hypoglycemia risk with a long life expectancy.”

In the paper

“BGM is thus an integral component of effective therapy of patients taking insulin.”

In the paper

“New data support the premise that increased TIR correlates with the risk of complications.”

What the sources say

• Not checked yetcites (30)(31)(32)

In the paper

“Therefore, achieving A1C targets of <7% (53 mmol/mol) has been shown to reduce microvascular complications of type 1 and type 2 diabetes when instituted early in the course of disease (2,48).”

What the sources say

• Not checked yetcites [2] Laiteerapong, 2019, The legacy effect in type 2 diabetes: impact of early glycemic control on future complications (the Diabetes & Aging Study), Diabetes Care source
• Not checked yetcites [48] Lind, 2019, HbA1c level as a risk factor for retinopathy and nephropathy in children and adults with type 1 diabetes: Swedish population based cohort study, BMJ source

In the paper

“Follow-up of the DCCT cohorts in the Epidemiology of Diabetes Interventions and Complications (EDIC) study (42,43) demonstrated persistence of these microvascular benefits over two decades despite the fact that the glycemic separation between the treatment groups diminished and disappeared during follow-up.”

What the sources say

• Not checked yetcites [42] Diabetes Control and Complications Trial (DCCT)/Epidemiology of Diabetes Interventions and Complications (EDIC) Research Group, 2015, Effect of intensive diabetes therapy on the progression of diabetic retinopathy in patients with type 1 diabetes: 18 years of follow-up in the DCCT/EDIC, Diabetes source
• Not checked yetcites [43] Diabetes Control and Complications Trial/Epidemiology of Diabetes Interventions and Complications Research Group, 2000, Retinopathy and nephropathy in patients with type 1 diabetes four years after a trial of intensive therapy, N Engl J Med source

In the paper

“The Diabetes Control and Complications Trial (DCCT) (33), a prospective randomized controlled trial of intensive (mean A1C about 7% [53 mmol/mol]) versus standard (mean A1C about 9% [75 mmol/mol]) glycemic control in people with type 1 diabetes, showed definitively that better glycemic control is associated with 50-76% reductions in rates of development and progression of microvascular (retinopath”

What the sources say

• Not checked yetcites [33] Diabetes Control and Complications Trial Research Group, 1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med source

In the paper

“However, 10-year follow-up of the VADT cohort (64) did demonstrate a reduction in the risk of cardiovascular events (52.7 [control group] vs. 44.1 [intervention group] events per 1,000 person-years) with no benefit in cardiovascular or overall mortality.”

What the sources say

• Not checked yetcites [64] Hayward, 2015, Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“The endstage renal disease rate was lower in the intensive treatment group over follow-up.”

What the sources say

• Not checked yetcites [63] Zoungas, 2014, Follow-up of blood-pressure lowering and glucose control in type 2 diabetes, N Engl J Med source

In the paper

“In the DCCT, there was a trend toward lower risk of CVD events with intensive control.”

What the sources say

• Not checked yetcites [33] Diabetes Control and Complications Trial Research Group, 1993, The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus, N Engl J Med source

In the paper

“Longer-term follow-up has shown no evidence of cardiovascular benefit, or harm, in the ADVANCE trial (63).”

What the sources say

• Not checked yetcites [63] Zoungas, 2014, Follow-up of blood-pressure lowering and glucose control in type 2 diabetes, N Engl J Med source

In the paper

“However, 10-year follow-up of the VADT cohort (64) did demonstrate a reduction in the risk of cardiovascular events (52.7 [control group] vs. 44.1 [intervention group] events per 1,000 person-years) with no benefit in cardiovascular or overall mortality.”

What the sources say

• Not checked yetcites [64] Hayward, 2015, Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“In the 9-year post-DCCT follow-up of the EDIC cohort, participants previously randomized to the intensive arm had a significant 57% reduction in the risk of nonfatal myocardial infarction (MI), stroke, or cardiovascular death compared with those previously randomized to the standard arm (54).”

What the sources say

• Not checked yetcites [54] Nathan, 2005, Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes, N Engl J Med source

In the paper

“Mortality findings in ACCORD (62) and subgroup analyses of VADT (66) suggest that the potential risks of intensive glycemic control may outweigh its benefits in higher-risk individuals.”

What the sources say

• Not checked yetcites [62] Gerstein, 2008, Effects of intensive glucose lowering in type 2 diabetes, N Engl J Med source
• Not checked yetcites [66] Duckworth, 2011, The duration of diabetes affects the response to intensive glucose control in type 2 subjects: the VA Diabetes Trial, J Diabetes Complications source

In the paper

“Findings from these studies suggest caution is needed in treating diabetes to near-normal A1C goals in people with long-standing type 2 diabetes with or at significant risk of CVD.”

In the paper

“ACCORD, ADVANCE, and VADT suggested no significant reduction in CVD outcomes with intensive glycemic control in participants followed for shorter durations (3.5-5.6 years) and who had more advanced type 2 diabetes and CVD risk than the UKPDS participants.”

What the sources say

• Not checked yetcites (50)(51)(52)

In the paper

“However, 10-year follow-up of the VADT cohort (64) did demonstrate a reduction in the risk of cardiovascular events (52.7 [control group] vs. 44.1 [intervention group] events per 1,000 person-years) with no benefit in cardiovascular or overall mortality.”

What the sources say

• Not checked yetcites [64] Hayward, 2015, Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“Analysis of the ACCORD data did not identify a clear explanation for the excess mortality in the intensive treatment arm (62).”

What the sources say

• Not checked yetcites [62] Gerstein, 2008, Effects of intensive glucose lowering in type 2 diabetes, N Engl J Med source

In the paper

“Heterogeneity of mortality effects across studies was noted, which may reflect differences in glycemic targets, therapeutic approaches, and, importantly, population characteristics (65).”

What the sources say

• Not checked yetcites [65] Turnbull, 2009, Intensive glucose control and macrovascular outcomes in type 2 diabetes, Diabetologia source

In the paper

“In people with diabetes, surrogate measures of vascular pathology, such as endothelial dysfunction, are negatively affected by postprandial hyperglycemia.”

In the paper

“Thus, a goal that might be appropriate for an individual early in the course of their diabetes may change over time.”

In the paper

“Over time, comorbidities may emerge, decreasing life expectancy and thereby decreasing the potential to reap benefits from intensive control.”

In the paper

“As discussed further below, severe hypoglycemia is a potent marker of high absolute risk of cardiovascular events and mortality (69).”

What the sources say

• Not checked yetcites [69] Lee, 2018, The association of severe hypoglycemia with incident cardiovascular events and mortality in adults with type 2 diabetes, Diabetes Care source

In the paper

“Additionally, a randomized controlled trial in patients with known CVD found no CVD benefit of insulin treatment plans targeting postprandial glucose compared with those targeting preprandial glucose (73).”

What the sources say

• Not checked yetcites [73] Raz, 2009, Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial, Diabetes Care source

In the paper

“Individuals with a long duration of diabetes, a known history of hypoglycemia, advanced atherosclerosis, or advanced age/frailty may benefit from less aggressive targets (67,68).”

What the sources say

• Not checked yetcites [67] Lipska, 2015, Potential overtreatment of diabetes mellitus in older adults with tight glycemic control, JAMA Intern Med source
• Not checked yetcites [68] Vijan, 2014, Effect of patients’ risks and preferences on health gains with plasma glucose level lowering in type 2 diabetes mellitus, JAMA Intern Med source

In the paper

“Elevated postchallenge (2-h oral glucose tolerance test) glucose values have been associated with increased cardiovascular risk independent of fasting plasma glucose in some epidemiologic studies, whereas intervention trials have not shown postprandial glucose to be a cardiovascular risk factor independent of A1C.”

What the sources say

• Not checked yetcites [72] American Diabetes Association, 2001, Postprandial blood glucose, Diabetes Care source
• Not checked yetcites [73] Raz, 2009, Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial, Diabetes Care source

In the paper

“Elevated postchallenge (2-h oral glucose tolerance test) glucose values have been associated with increased cardiovascular risk independent of fasting plasma glucose in some epidemiologic studies, whereas intervention trials have not shown postprandial glucose to be a cardiovascular risk factor independent of A1C.”

What the sources say

• Not checked yetcites [72] American Diabetes Association, 2001, Postprandial blood glucose, Diabetes Care source
• Not checked yetcites [73] Raz, 2009, Effects of prandial versus fasting glycemia on cardiovascular outcomes in type 2 diabetes: the HEART2D trial, Diabetes Care source

In the paper

“Newly diagnosed patients and/or those without comorbidities that limit life expectancy may benefit from intensive control proven to prevent microvascular complications.”

In the paper

“In all three trials, severe hypoglycemia was significantly more likely in participants who were randomly assigned to the intensive glycemic control arm.”

What the sources say

• Not checked yetcites [62] Gerstein, 2008, Effects of intensive glucose lowering in type 2 diabetes, N Engl J Med source
• Not checked yetcites [63] Zoungas, 2014, Follow-up of blood-pressure lowering and glucose control in type 2 diabetes, N Engl J Med source
• Not checked yetcites [64] Hayward, 2015, Follow-up of glycemic control and cardiovascular outcomes in type 2 diabetes, N Engl J Med source

In the paper

“As outlined in more detail in Section 9, “Pharmacologic Approaches to Glycemic Treatment,” and Section 10, “Cardiovascular Disease and Risk Management,” the cardiovascular benefits of SGLT2 inhibitors or GLP-1 receptor agonists are not contingent upon A1C lowering; therefore, initiation can be considered in people with type 2 diabetes and CVD independent of the current A1C or A1C goal or metformin”

In the paper

“However, outcome studies have shown A1C to be the primary predictor of complications, and landmark trials of glycemic control such as the DCCT and UKPDS relied overwhelmingly on preprandial BGM.”

In the paper

“However, outcome studies have shown A1C to be the primary predictor of complications, and landmark trials of glycemic control such as the DCCT and UKPDS relied overwhelmingly on preprandial BGM.”

In the paper

“Thus, a finite period of intensive control to near-normal A1C may yield enduring benefits even if control is subsequently deintensified as patient characteristics change.”

In the paper

“Both DCCT/ EDIC and UKPDS demonstrated metabolic memory, or a legacy effect, in which a finite period of intensive control yielded benefits that extended for decades after that control ended.”

In the paper

“Conversely, in a substudy of the ACCORD trial, cognitive impairment at baseline or decline in cognitive function during the trial was significantly associated with subsequent episodes of level 3 hypoglycemia (85).”

What the sources say

• Not checked yetcites [85] Punthakee, 2012, Poor cognitive function and risk of severe hypoglycemia in type 2 diabetes: post hoc epidemiologic analysis of the ACCORD trial, Diabetes Care source

In the paper

“Level 3 hypoglycemia was associated with mortality in participants in both the standard and the intensive glycemia arms of the ACCORD trial, but the relationships between hypoglycemia, achieved A1C, and treatment intensity were not straightforward.”

In the paper

“If a patient has level 2 hypoglycemia without adrenergic or neuroglycopenic symptoms, they likely have hypoglycemia unawareness (discussed further below).”

What the sources say

• Not checked yetcites [75] Polonsky, 2021, “Hyperglycemia aversiveness”: investigating an overlooked problem among adults with type 1 diabetes, J Diabetes Complications source
• Not checked yetcites [79] Amiel, 2022, A parallel randomised controlled trial of the Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised self-care (HARPdoc), Nat Commun source

In the paper

“Studies of rates of level 3 hypoglycemia that rely on claims data for hospitalization, emergency department visits, and ambulance use substantially underestimate rates of level 3 hypoglycemia (87) yet reveal a high burden of hypoglycemia in adults over 60 years of age in the community (88).”

What the sources say

• Not checked yetcites [87] Karter, 2018, Surveillance of hypoglycemia—limitations of emergency department and hospital utilization data, JAMA Intern Med source

In the paper

“African American individuals are at substantially increased risk of level 3 hypoglycemia (88,89).”

What the sources say

• Not checked yetcites [88] Lee, 2017, risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) study, Diabetes Care source
• Not checked yetcites [89] Karter, 2017, High rates of severe hypoglycemia among African American patients with diabetes: the surveillance, prevention, and Management of Diabetes Mellitus (SUPREME-DM) network, J Diabetes Complications source

In the paper

“Evidence from DCCT/EDIC, which involved adolescents and younger adults with type 1 diabetes, found no association between frequency of level 3 hypoglycemia and cognitive decline (86).”

What the sources say

• Not checked yetcites [86] Jacobson, 2007, Long-term effect of diabetes and its treatment on cognitive function, N Engl J Med source

In the paper

“An association between selfreported level 3 hypoglycemia and 5-year mortality has also been reported in clinical practice (91).”

What the sources say

• Not checked yetcites [91] McCoy, 2012, Increased mortality of patients with diabetes reporting severe hypoglycemia, Diabetes Care source

In the paper

“Young children with type 1 diabetes and the elderly, including those with type 1 and type 2 diabetes (84,93), are noted as particularly vulnerable to hypoglycemia because of their reduced ability to recognize hypoglycemic symptoms and effectively communicate their needs.”

What the sources say

• Not checked yetcites [84] Whitmer, 2009, Hypoglycemic episodes and risk of dementia in older patients with type 2 diabetes mellitus, JAMA source
• Not checked yetcites [93] DuBose, 2016, Hypoglycemia in older adults with type 1 diabetes, Diabetes Technol Ther source

In the paper

“Glucose variability is also associated with an increased risk for hypoglycemia (92).”

What the sources say

• Not checked yetcites [92] Cahn, 2022, Machine learning based study of longitudinal HbA1c trends and their association with all-cause mortality: analyses from a national diabetes registry, Diabetes Metab Res Rev source

In the paper

“Studies of rates of level 3 hypoglycemia that rely on claims data for hospitalization, emergency department visits, and ambulance use substantially underestimate rates of level 3 hypoglycemia (87) yet reveal a high burden of hypoglycemia in adults over 60 years of age in the community (88).”

What the sources say

• Not checked yetcites [88] Lee, 2017, risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) study, Diabetes Care source

In the paper

“In addition to age and race, other important risk factors found in a community-based epidemiologic cohort of older adults with type 2 diabetes include insulin use, poor or moderate versus good glycemic control, albuminuria, and poor cognitive function (88).”

What the sources say

• Not checked yetcites [88] Lee, 2017, risk factors for severe hypoglycemia in black and white adults with diabetes: the Atherosclerosis Risk in Communities (ARIC) study, Diabetes Care source

In the paper

“Level 3 hypoglycemia was associated with mortality in participants in both the standard and the intensive glycemia arms of the ACCORD trial, but the relationships between hypoglycemia, achieved A1C, and treatment intensity were not straightforward.”

In the paper

“These findings support that premeal glucose targets may be relaxed without undermining overall glycemic control as measured by A1C.”

In the paper

“An association of level 3 hypoglycemia with mortality was also found in the ADVANCE trial (90).”

What the sources say

• Not checked yetcites [90] Zoungas, 2010, Severe hypoglycemia and risks of vascular events and death, N Engl J Med source

In the paper

“CGM with automated low glucose suspend and hybrid closed-loop systems have been shown to be effective in reducing hypoglycemia in type 1 diabetes (95).”

What the sources say

• Not checked yetcites [95] Bergenstal, 2013, Threshold-based insulin-pump interruption for reduction of hypoglycemia, N Engl J Med source

In the paper

“Conversely, some individuals with type 1 diabetes or type 2 diabetes and hypoglycemia who have a fear of hyperglycemia are resistant to relaxation of glycemic targets (74)(75)(76)(77)(78)(79)(80)(81)(82)(83).”

What the sources say

• Not checked yetcites [74] Agiostratidou, 2017, Standardizing clinically meaningful outcome measures beyond HbA1c for type 1 diabetes: a consensus report of the American Association of Clinical Endocrinologists, the American Association of Diabetes Educators, the American Diabetes Association, the Endocrine Society, JDRF International, The Leona M. and Harry B. Helmsley Charitable Trust, the Pediatric Endocrine Society, and the T1D Exchange, Diabetes Care source
• Not checked yetcites [75] Polonsky, 2021, “Hyperglycemia aversiveness”: investigating an overlooked problem among adults with type 1 diabetes, J Diabetes Complications source
• Not checked yetcites [76] Ghandi, 2021, A comparison of validated methods used to assess impaired awareness of hypoglycaemia in type 1 diabetes: an observational study, Diabetes Ther source
• Not checked yetcites [77] Li, 2019, Early hypoglycaemia and adherence after basal insulin initiation in a nationally representative sample of Medicare beneficiaries with type 2 diabetes, Diabetes Obes Metab source
• Not checked yetcites [78] Hendrieckx, 2019, Impact of severe hypoglycaemia on psychological outcomes in adults with type 2 diabetes: a systematic review, Diabet Med source
• Not checked yetcites [79] Amiel, 2022, A parallel randomised controlled trial of the Hypoglycaemia Awareness Restoration Programme for adults with type 1 diabetes and problematic hypoglycaemia despite optimised self-care (HARPdoc), Nat Commun source
• Not checked yetcites [80] Khunti, 2017, Impact of hypoglycaemia on patient-reported outcomes from a global, 24-country study of 27,585 people with type 1 and insulin-treated type 2 diabetes, Diabetes Res Clin Pract source
• Not checked yetcites [81] Choudhary, 2018, Hypoglycaemia in type 1 diabetes: technological treatments, their limitations and the place of psychology, Diabetologia source
• Not checked yetcites [82] Hopkins, 2012, Improved biomedical and psychological outcomes 1 year after structured education in flexible insulin therapy for people with type 1 diabetes: the U.K. DAFNE experience, Diabetes Care source
• Not checked yetcites [83] Yang, 2019, Determining the optimal fasting glucose target for patients with type 2 diabetes: results of the multicentre, open-label, randomized-controlled FPG GOAL trial, Diabetes Obes Metab source

In the paper

“In 2015, the ADA changed its preprandial glycemic target from 70-130 mg/dL (3.9-7.2 mmol/L) to 80-130 mg/dL (4.4-7.2 mmol/L).”

In the paper

“The acute glycemic response correlates better with the glucose content of food than with the carbohydrate content of food.”

What the sources say

• Not checked yetcites [98] McTavish, 2011, Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial, Pediatr Diabetes source
• Not checked yetcites [99] McTavish, 2018, Weight-based carbohydrate treatment of hypoglycaemia in people with type 1 diabetes using insulin pump therapy: a randomized crossover clinical trial, Diabet Med source
• Not checked yetcites [100] Georgakopoulos, 1990, Recovery from insulin-induced hypoglycemia after saccharose or glucose administration, Clin Physiol Biochem

In the paper

“Ongoing insulin activity or insulin secretagogues may lead to recurrent hypoglycemia unless more food is ingested after recovery.”

In the paper

“Hypoglycemia treatment requires ingestion of glucose-or carbohydratecontaining foods (98-100).”

What the sources say

• Not checked yetcites [98] McTavish, 2011, Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial, Pediatr Diabetes source
• Not checked yetcites [99] McTavish, 2018, Weight-based carbohydrate treatment of hypoglycaemia in people with type 1 diabetes using insulin pump therapy: a randomized crossover clinical trial, Diabet Med source
• Not checked yetcites [100] Georgakopoulos, 1990, Recovery from insulin-induced hypoglycemia after saccharose or glucose administration, Clin Physiol Biochem

In the paper

“In type 2 diabetes, ingested protein may increase insulin response without increasing plasma glucose concentrations (101).”

What the sources say

• Not checked yetcites [101] Layman, 2008, Protein in optimal health: heart disease and type 2 diabetes, Am J Clin Nutr source

In the paper

“This change reflects the results of the ADAG study, which demonstrated that higher glycemic targets corresponded to A1C goals ( 14).”

What the sources say

• Not checked yetcites [14] Wei, 2014, Empirically establishing blood glucose targets to achieve HbA1c goals, Diabetes Care source

In the paper

“Pure glucose is the preferred treatment, but any form of carbohydrate that contains glucose will raise blood glucose.”

What the sources say

• Not checked yetcites [98] McTavish, 2011, Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial, Pediatr Diabetes source
• Not checked yetcites [99] McTavish, 2018, Weight-based carbohydrate treatment of hypoglycaemia in people with type 1 diabetes using insulin pump therapy: a randomized crossover clinical trial, Diabet Med source
• Not checked yetcites [100] Georgakopoulos, 1990, Recovery from insulin-induced hypoglycemia after saccharose or glucose administration, Clin Physiol Biochem

In the paper

“Overall, realtime CGM appears to be a useful tool for decreasing time spent in a hypoglycemic range in people with impaired awareness.”

In the paper

“Real-time CGM studies can be divided into studies with elevated A1C with the primary end point of A1C reduction and studies with A1C near target with the primary end point of reduction in hypoglycemia (98, 109-124).”

What the sources say

• Not checked yetcites [98] McTavish, 2011, Effective treatment of hypoglycemia in children with type 1 diabetes: a randomized controlled clinical trial, Pediatr Diabetes source
• Not checked yetcites [109] Heinemann, 2018, Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial, Lancet source
• Not checked yetcites [110] Beck, 2017, Effect of continuous glucose monitoring on glycemic control in adults with type 1 diabetes using insulin injections: the DIAMOND randomized clinical trial, JAMA source
• Not checked yetcites [111] Sequeira, 2013, Continuous glucose monitoring pilot in low-income type 1 diabetes patients, Diabetes Technol Ther source
• Not checked yetcites [112] Tumminia, 2015, Efficacy of real-time continuous glucose monitoring on glycaemic control and glucose variability in type 1 diabetic patients treated with either insulin pumps or multiple insulin injection therapy: a randomized controlled crossover trial, Diabetes Metab Res Rev source
• Not checked yetcites [113] Bolinder, 2016, Novel glucose-sensing technology and hypoglycaemia in type 1 diabetes: a multicentre, non-masked, randomised controlled trial, Lancet source
• Not checked yetcites [114] Hermanns, 2014, The impact of continuous glucose monitoring on low interstitial glucose values and low blood glucose values assessed by point-of-care blood glucose meters: results of a crossover trial, J Diabetes Sci Technol source
• Not checked yetcites [115] Reddy, 2018, A randomized controlled pilot study of continuous glucose monitoring and flash glucose monitoring in people with Type 1 diabetes and impaired awareness of hypoglycaemia, Diabet Med source
• Not checked yetcites [116] Riddlesworth, 2017, Hypoglycemic event frequency and the effect of continuous glucose monitoring in adults with type 1 diabetes using multiple daily insulin injections, Diabetes Ther source
• Not checked yetcites [117] van Beers, 2016, Continuous glucose monitoring for patients with type 1 diabetes and impaired awareness of hypoglycaemia (IN CONTROL): a randomised, open-label, crossover trial, Lancet Diabetes Endocrinol source

In the paper

“With the advent of sensor-augmented CGM and CGM-assisted pump therapy, there has been a promise of alarm-based prevention of hypoglycemia (108,109).”

What the sources say

• Not checked yetcites [108] Hermanns, 2019, Impact of CGM on the management of hypoglycemia problems: overview and secondary analysis of the HypoDE study, J Diabetes Sci Technol source
• Not checked yetcites [109] Heinemann, 2018, Real-time continuous glucose monitoring in adults with type 1 diabetes and impaired hypoglycaemia awareness or severe hypoglycaemia treated with multiple daily insulin injections (HypoDE): a multicentre, randomised controlled trial, Lancet source

In the paper

“For studies targeting hypoglycemia, most studies demonstrated a significant reduction in time spent between 54 and 70 mg/dL.”

In the paper

“For people with type 2 diabetes, other strategies to assist them with insulin dosing can improve A1C with minimal hypoglycemia (133,134).”

What the sources say

• Not checked yetcites [133] Bergenstal, 2019, Automated insulin dosing guidance to optimise insulin management in patients with type 2 diabetes: a multicentre, randomised controlled trial, Lancet source
• Not checked yetcites [134] Kitabchi, 2009, Hyperglycemic crises in adult patients with diabetes, Diabetes Care source

In the paper

“A corollary to this “vicious cycle” is that several weeks of avoidance of hypoglycemia has been demonstrated to improve counterregulation and hypoglycemia awareness in many people with diabetes (106).”

What the sources say

• Not checked yetcites [106] Cryer, 2004, Diverse causes of hypoglycemia-associated autonomic failure in diabetes, N Engl J Med source

In the paper

“In people with type 1 and type 2 diabetes with A1C above target, CGM improved A1C between 0.3 and 0.6%.”

In the paper

“In type 1 diabetes and severely insulindeficient type 2 diabetes, hypoglycemia unawareness (or hypoglycemia-associated autonomic failure) can severely compromise stringent diabetes control and quality of life.”

In the paper

“A report in people with type 1 diabetes over the age of 60 years revealed a small but statistically significant decrease in hypoglycemia (125).”

What the sources say

• Not checked yetcites [125] Pratley, 2020, Effect of continuous glucose monitoring on hypoglycemia in older adults with type 1 diabetes: a randomized clinical trial, JAMA source